title: Pterocarpans and flavanones from Sophora flavescens displaying potent neuraminidase inhibition.
abstract: Pterocarpans (1-3) and flavanones (4-10) were isolated from Sophora flavescens and screened for their ability to inhibit neuraminidase (an enzyme crucial in the proliferation of the influenza virus). The majority of inhibitors were shown to have IC(50) values of 20 microM or below. Interestingly, pterocarpan 1 emerged as the best inhibitor with an IC(50) of 1.4 microM. We were thus able to prove that the pterocarpan skeleton is a new class of lead structure for neuraminidase inhibitors. Our studies reveal that the IC(50) has a marked dependence upon structure in the case of the pterocarpans but much less so for the flavanones. Kinetic analysis disclosed that all inhibitors are noncompetitive. Our molecular docking experiment resulted that the most potent pterocarpan-derived inhibitor 1 may bind to another binding pocket adjacent to the active site.
authors.affiliation: Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Curtis-Long
authors.forename: Jin Hyo
authors.initials: JH
authors.lastname: Kim
authors.forename: Seong Hun
authors.initials: SH
authors.lastname: Jeong
authors.forename: Min Suk
authors.initials: MS
authors.lastname: Yang
authors.forename: Keun Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D003013:Clostridium / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000187:drug effects*; D010946:Plants, Medicinal / Q000737:chemistry*; D036343:Pterocarpans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D029909:Sophora / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D044950:Flavanones; D036343:Pterocarpans; D009439:Neuraminidase